| Title: | Adjusting for common variant polygenic scores improves yield in rare variant association analyses |
| Journal: | Nature Genetics |
| Published: | 23 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36959364/ |
| DOI: | https://doi.org/10.1038/s41588-023-01342-w |
| URL: | https://doi.org/10.1101/2021.10.18.464866 |
Publication 11232
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
With the emergence of large-scale sequencing data, methods for improving power in rare variant association tests are needed. Here we show that adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests across 65 quantitative traits in the UK Biobank (up to 20% increase at α = 2.6 × 10−6), without marked increases in false-positive rates or genomic inflation. Benefits were seen for various models, with the largest improvements seen for efficient sparse mixed-effects models. Our results illustrate how polygenic score adjustment can efficiently improve power in rare variant association discovery.</p>
8 Authors
- Sean J. Jurgens
- James P. Pirruccello
- Seung Hoan Choi
- Valerie N. Morrill
- Mark Chaffin
- Steven A. Lubitz
- Kathryn L. Lunetta
- Patrick T. Ellinor
1 Application
| Application ID | Title |
|---|---|
| 17488 | Understanding the Genetic Basis of Cardiac Arrhythmias |
Enabling scientific discoveries that improve human health